study of eos-448 with standard of care and/or investigational therapies in participants with advanced solid tumors

Conditions: Advanced Cancer; Lung Cancer; Head and Neck Cancer; Melanoma

Summary: this is a multicenter, open-label, phase i/ii basket study, evaluating the safety, tolerability, rp2d, pharmacokinetics, pharmacodynamics and antitumor activity of eos-448 (also known as gsk4428859a or belrestotug) combined with standard of care and/or with investigational therapies in participants with advanced solid tumors.

the combinations evaluated will be: * eos-448 combined with pembrolizumab, an anti-pd-1 antibody * eos-448 combined with inupadenant an investigational adenosine a2a receptor antagonist * eos-448 combined with dostarlimab an anti-pd-1 antibody * inupadenant combined with dostarlimab * eos-448 combined with inupadenant and dostarlimab * eos-448 combined with dostarlimab and standard of care chemotherapies in participants with nsclc

Eligibility criteria:
inclusion criteria: * provide a signed written informed consent for the trial * have measurable disease, per recist v1.1 * have an eastern cooperative oncology group (ecog) performance status of grade 0 or 1. * have adequate organ functions * part 1a/1b/1c/1d/1e/1f: have histologically or cytologically confirmed advanced or metastatic solid tumor for whom no standard treatment with survival benefit is available part 1g (nsclc): * have a histologically confirmed or cytologically confirmed previously untreated stage iv or stage iii not amenable to curative chemoradiotherapy or surgery (ajcc 8th edition) nonsquamous nsclc or squamous nsclc. * are eligible to receive anti-pd(l)1 therapy combined with chemotherapy in first line metastatic setting part 2 (h\&n cancer) * have histologically or cytologically confirmed recurrent advanced or metastatic head and neck squamous cell carcinoma considered incurable by local therapies * pd-l1 status positive exclusion criteria: * have received any anti-cancer therapy within 4 weeks prior to the first dose * have received a live vaccine within 30 days prior to the first dose * have known primary cns cancer. * have known cns metastases unless previously treated and well controlled for at least 1 month * have concomitant second malignancies unless a complete remission was achieved at least 2 years before study entry * have a history of grade ≥ 2 pneumonitis, active autoimmune disease, or persistent immune-mediated toxicity caused by immune checkpoint inhibitor therapy of grade ≥ 2 * have toxicity (except for alopecia) related to prior anti-cancer therapy and/or surgery unless the toxicity is either resolved, returned to baseline or grade 1, or deemed irreversible. * have uncontrolled or significant cardiovascular disease * part 1: major surgery within 3 weeks before initiating treatment * part 1: have received prior radiotherapy within 2 weeks of start of study treatment * part 2 (h\&n cancer): * have received prior immunotherapy with an anti-pd-1, anti-pd-l1, anti-pd-l2, anti-cd137, or anti-cytotoxic t-lymphocyte-associated antigen-4 (ctla-4) antibody (including ipilimumab or any other antibody or drug specifically targeting t-cell co-stimulation or checkpoint pathways). * have received prior chemotherapy administered in the recurrent advanced or metastatic setting (except for systemic therapy completed \> 6 months prior to screening if given as part of multimodal treatment for locally advanced disease)

Keywords: eos884448 gsk4428859a tigit anti-tigit eos-448 pembrolizumab dostarlimab inupadenant a2a receptor antagonist eos-850 eos100850 anti-pd-1 monoclonal antibody belrestotug